The Bommarius lab offers a summer position as of May 6, 2013, for an advanced undergraduate or graduate student, or recent graduate to complete a DOE STTR-SBIR phase II project on the
Removal of
ammonia and water to enhance yield of beta-lactam syntheses through suppression
of secondary hydrolysis
The
project combines the use of biocatalysts to synthesize beta-lactam antibiotics,
specifically ampicillin as a model, with the use of a hollow-fiber membrane
contactor to withdraw ammonia, the by-product of the synthesis:
PGA
D-phenylglycine-amide +
6-aminopenicillanic acid ® ampicillin +
NH3/NH4+
Hydrolysis PGA
side reaction: D-phenylglycine-amide + H2O ® D-phenylglycine + NH3/NH4+
PGA = penicillin
G acylase.
If successful, such a novel process to
synthesize beta-lactams could lead to less expensive anti-infectives. The focus
of the work will be on the transport of ammonia through the membrane. The membrane module
itself will be supplied by our collaborator, Compact Membrane Systems (CMS) of
Newark, DE. Also, some parts of the
characterization are envisioned to take place in CMS’ labs in Newark, DE.
We
have developed a variant of penicillin G acylase (PGA) in the Bommarius lab
that strongly favors synthesis over hydrolysis.
Enzyme is available, the assays are worked out. After characterization of ammonia transport
through the membrane, we will run the PGA-catalyzed reaction to ampicillin
through the hollow-fiber membrane contactor, remove ammonia, and seek to optimize yield and selectivity.
In
summary, the work entails the following items:
1.
Characterization
of transport of ammonia through the hollow-fiber membrane module from aqueous
solution, mainly as function of concentration, pH value & transmembrane
pressure
2.
Ampicillin
synthesis in a membrane contactor loop reactor; ampicillin yield as a function
of substrate concentrations, pH value, and selected other variables.
Publication
opportunity is envisioned and is strongly encouraged. Interested?: Please email resume to Prof. Andreas S.
Bommarius (andreas.bommarius@chbe.gatech.edu).
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